Critical windows of fluoride neurotoxicity in Canadian children

Farmus L, Till C, Green R, Hornung R, Martinez-Mier EA, Ayotte P, Muckle G, Lanphear B, Flora D


Environmental Research


Background

Fluoride has been associated with IQ deficits during early brain development, but the period in which children are most sensitive is unknown.


Objective

We assessed effects of fluoride on IQ scores across prenatal and postnatal exposure windows.


Methods

We used repeated exposures from 596 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals pregnancy and birth cohort. Fluoride was measured in urine (mg/L) collected from women during pregnancy and in their children between 1.9 and 4.4 years; urinary fluoride was adjusted for specific gravity. We estimated infant fluoride exposure (mg/day) using water fluoride concentration and duration of formula-feeding over the first year of life. Intelligence was assessed at 3–4 years using the Wechsler Preschool and Primary Scale of Intelligence-III. We used generalized estimating equations to examine the associations between fluoride exposures and IQ, adjusting for covariates. We report results based on standardized exposures given their varying units of measurement.


Results

The association between fluoride and performance IQ (PIQ) significantly differed across prenatal, infancy, and childhood exposure windows collapsing across child sex (p = .001). The strongest association between fluoride and PIQ was during the prenatal window, B = −2.36, 95% CI: −3.63, −1.08; the association was also significant during infancy, B = −2.11, 95% CI: −3.45, −0.76, but weaker in childhood, B = −1.51, 95% CI: −2.90, −0.12. Within sex, the association between fluoride and PIQ significantly differed across the three exposure windows (boys: p = .01; girls: p = .01); among boys, the strongest association was during the prenatal window, B = −3.01, 95% CI: −4.60, −1.42, whereas among girls, the strongest association was during infancy, B = −2.71, 95% CI: −4.59, −0.83. Full-scale IQ estimates were weaker than PIQ estimates for every window. Fluoride was not significantly associated with Verbal IQ across any exposure window.


Conclusion

Associations between fluoride exposure and PIQ differed based on timing of exposure. The prenatal window may be critical for boys, whereas infancy may be a critical window for girls.